Hepatitis E virus (HEV) is believed to be the most common cause of acute hepatitis and jaundice in the world. Although HEV genotype 1 and 2 infect only human beings, genotypes 3 and 4 are zoonotic viruses that also infect swine and other animal species. Acute hepatitis E usually is self-limited. However, HEV genotype 3 can persist in immunocompromised patients, especially organ transplant recipients, causing chronic hepatitis, which may progress to cirrhosis and liver graft failure. Reduction of immunosuppressive therapy, ribavirin (RBV), or pegylated interferon-α have been used with varying success, allowing for viral clearance in up to 78% of patients. However, failure of RBV has been described. Hence, safer and more effective treatment options are needed.